2019-10-17

Bacterial infections may cause disease and death. Antimicrobials kill bacteria protecting the infected patients and reducing the risk of morbidity and mortality caused by bacteria. The antibiotics may lose their antibacterial activity when they become resistant to bacteria. The resistance to different antibiotics in bacteria is named multidrug-resistance.
 

TYPES OF ANTIMICROBIAL RESISTANCE-

Gram-negative bacilli, especially Escherichia coli, Klebsiella, Enterobacter, Salmonella, Shigella, Pseudomonas, Streptococcus, and Haemophilus influenzae type b, may become resistant. Amikacin ampicillin, amoxicillin, amoxiclav, cefuroxime, cefotaxime, ceftazidime, cefoperazone tetracycline, chloramphenicol, ciprofloxacin, and gentamicin may cause bacterial- resistance. Resistance to bacteria for several pathogens makes complications in the treatment of infections caused by them.

Salmonella strains may become resistant to ampicillin, cephalotin, ceftriaxone, gentamicin, amikacin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Shigella strains may become resistant to ampicillin, cotrimoxazole, chloramphenicol, and streptomycin.

Multidrug-resistance of Streptococcus pneumoniae may be due to β-lactams, macrolides, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.

Multidrug-resistance of Pseudomonas aeruginosa may become resistant to β-lactams, chloramphenicol, trimethoprim-sulfamethoxazole, and tetracycline. The antibacterial activity against Haemophilus strains may occur with ampicillin, sulbactam-ampicillin, trimethoprim-sulfamethoxazole, gentamicin, chloramphenicol, and ciprofloxacin.

Multidrug-resistance of the Klebsiella species may be due with ampicillin, cefotaxime, cefuroxime, co-amxilav, mezlocillin, chloramphenicol, gentamicin, and ceftazidime.

Multidrug-resistance of Escherichia coli may be caused by ampicillin, cotrimoxazole, chloramphenicol, ceftriaxone, and ceftazidime. Vibrio cholera may become resistant to cotrimoxazole, chloramphenicol, ampicillin, with least resistance to erythromicin, tetracycline, and ciprofloxacin.

MECHANISMS OF ANTIMICROBIAL RESISTANCE

1) Enzymatic degradation of antibacterial drugs- alteration of bacterial proteins that are antimicrobial targets, and (3) changes in membrane permeability to antibiotics

OVERVIEW ON MECHANISM OF ANTIBACTERIAL RESISTANCE 

In general, the reasons for increasing resistance levels include the following:

• suboptimal use of antimicrobials for prophylaxis and treatment of infection
• noncompliance with infection-control practices
• prolonged hospitalization, increased number and duration of intensive care-unit stays
• multiple co morbidities in hospitalized patients
• increased use of invasive devices and catheters
• ineffective infection-control practices, transfer of colonized patients from hospital to hospital, grouping of colonized patients in long-term-care facilities
• antibiotic use in agriculture and household chores
• Increasing national and international travel 
•The level of antibiotic resistance is dependent on the following:
• the population of organisms that spontaneously acquire resistance mechanisms as a result of selective pressure either from antibiotic use.
• the rate of introduction from the community of those resistant organisms into health care settings.
• The proportion that is spread from person to person. All of these factors must be addressed in order to control the spread of antimicrobial-resistant organisms within health care settings. Community-acquired antimicrobial resistance is increasing in large part because of the widespread suboptimal use of antibiotics in the outpatient settings and the use of antibiotics in animal husbandry and agriculture.
 

MECHANISMS OF ACTION OF ANTIMICROBIAL AGENTS

In order to appreciate the mechanisms of resistance, it is important to understand how antimicrobial agents act. Antimicrobial agents act selectively on vital microbial functions with minimal effects or without affecting host functions. Different antimicrobial agents act in different ways. The understanding of these mechanisms as well as the chemical nature of the antimicrobial agents is crucial in the understanding of the ways how resistance against them.

CLASSIFICATION OF ANTI-MICROBIAL AGENTS- • 

Bacteriostatic antimicrobial- These agents only inhibit the growth or multiplication of the bacteria giving the immune system of the host time to clear them from the system. Complete elimination of the bacteria in this case, therefore, is dependent on the competence of the immune system.

• Bactericidal agents- They kill the bacteria and therefore with or without a competent immune system of the host, the bacteria will be dead. •

• However, the mechanism of action of antimicrobial agents can be categorized further based on the structure of the bacteria or the function that is affected by the agents. These include generally the following:

• Inhibition of the cell wall synthesis

• Inhibition of ribosome function

• Inhibition of nucleic acid synthesis

• Inhibition of foliate metabolism

• Inhibition of cell membrane function

MECHANISMS OF ANTIMICROBIAL RESISTANCES

 Prior to the 1990s, the problem of antimicrobial resistance was never taken to be such a threat to the management of infectious diseases. But gradually treatment failures were increasingly being seen in health care settings against first-line drugs and second-line drugs or more. Microorganisms were increasingly becoming resistant to ensure their survival against the arsenal of antimicrobial agents to which they were being bombarded. They achieved this through different means but primarily based on the chemical structure of the antimicrobial agent and the mechanisms through which the agents acted. The resistance mechanisms, therefore, depend on which specific pathways are inhibited by the drugs and the alternative ways available for those pathways that the organisms can modify to get a way around in order to survive.

Intrinsic or natural or passive whereby microorganisms naturally do not posses target sites for the drugs and therefore the drug does not affect them or they naturally have low permeability to those agents because of the differences in the chemical nature of the drug and the microbial membrane structures especially for those that require entry into the microbial cell in order to effect their action. An example of natural resistance is Pseudomonas aeruginosa, whose low membrane permeability is likely to be a main reason for its innate resistance to many antimicrobials. Other examples are the presence of genes affording resistance to self-produced antibiotics, the outer membrane of Gram-negative bacteria, absence of an uptake transport system for the antimicrobial or general absence of the target or reaction hit by the antimicrobial.

• Acquired or active resistance, the major mechanism of antimicrobial resistance, is the result of a specific evolutionary pressure to develop a counterattack mechanism against an antimicrobial or class of antimicrobials so that bacterial populations previously sensitive to antimicrobials become resistant. This type of resistance results from changes in the bacterial genome. Resistance in bacteria may be acquired by a mutation and passed vertically by selection to daughter cells . More commonly, resistance is acquired by horizontal transfer of resistance genes between strains and species. Exchange of genes is possible by transformation, transduction or conjugation. Acquired resistance mechanisms can occur through various ways.

Mechanisms for acquired resistance -

• the presence of an enzyme that inactivates the antimicrobial agent
• the presence of an alternative enzyme for the enzyme that is inhibited by the antimicrobial agent
• a mutation in the antimicrobial agent’s target, which reduces the binding of the antimicrobial agent
• post-transcriptional or post-translational modification of the antimicrobial agent’s target, which reduces binding of the antimicrobial agent
• reduced uptake of the antimicrobial agent
• active efflux of the antimicrobial agent overproduction of the target of the antimicrobial agent

The antibiotics may lose their antibacterial activity when they become resistant to bacteria.

Bacterial infections may cause disease and death. Antimicrobials kill bacteria protecting the infected patients and reducing the risk of morbidity and mortality caused by bacteria. The antibiotics may lose their antibacterial activity when they become resistant to bacteria. The resistance to different antibiotics in bacteria is named multidrug-resistance.
 

TYPES OF ANTIMICROBIAL RESISTANCE-

Gram-negative bacilli, especially Escherichia coli, Klebsiella, Enterobacter, Salmonella, Shigella, Pseudomonas, Streptococcus, and Haemophilus influenzae type b, may become resistant. Amikacin ampicillin, amoxicillin, amoxiclav, cefuroxime, cefotaxime, ceftazidime, cefoperazone tetracycline, chloramphenicol, ciprofloxacin, and gentamicin may cause bacterial- resistance. Resistance to bacteria for several pathogens makes complications in the treatment of infections caused by them.

Salmonella strains may become resistant to ampicillin, cephalotin, ceftriaxone, gentamicin, amikacin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline. Shigella strains may become resistant to ampicillin, cotrimoxazole, chloramphenicol, and streptomycin.

Multidrug-resistance of Streptococcus pneumoniae may be due to β-lactams, macrolides, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.

Multidrug-resistance of Pseudomonas aeruginosa may become resistant to β-lactams, chloramphenicol, trimethoprim-sulfamethoxazole, and tetracycline. The antibacterial activity against Haemophilus strains may occur with ampicillin, sulbactam-ampicillin, trimethoprim-sulfamethoxazole, gentamicin, chloramphenicol, and ciprofloxacin.

Multidrug-resistance of the Klebsiella species may be due with ampicillin, cefotaxime, cefuroxime, co-amxilav, mezlocillin, chloramphenicol, gentamicin, and ceftazidime.

Multidrug-resistance of Escherichia coli may be caused by ampicillin, cotrimoxazole, chloramphenicol, ceftriaxone, and ceftazidime. Vibrio cholera may become resistant to cotrimoxazole, chloramphenicol, ampicillin, with least resistance to erythromicin, tetracycline, and ciprofloxacin.

MECHANISMS OF ANTIMICROBIAL RESISTANCE

1) Enzymatic degradation of antibacterial drugs- alteration of bacterial proteins that are antimicrobial targets, and (3) changes in membrane permeability to antibiotics

OVERVIEW ON MECHANISM OF ANTIBACTERIAL RESISTANCE 

In general, the reasons for increasing resistance levels include the following:

• suboptimal use of antimicrobials for prophylaxis and treatment of infection
• noncompliance with infection-control practices
• prolonged hospitalization, increased number and duration of intensive care-unit stays
• multiple co morbidities in hospitalized patients
• increased use of invasive devices and catheters
• ineffective infection-control practices, transfer of colonized patients from hospital to hospital, grouping of colonized patients in long-term-care facilities
• antibiotic use in agriculture and household chores
• Increasing national and international travel 
•The level of antibiotic resistance is dependent on the following:
• the population of organisms that spontaneously acquire resistance mechanisms as a result of selective pressure either from antibiotic use.
• the rate of introduction from the community of those resistant organisms into health care settings.
• The proportion that is spread from person to person. All of these factors must be addressed in order to control the spread of antimicrobial-resistant organisms within health care settings. Community-acquired antimicrobial resistance is increasing in large part because of the widespread suboptimal use of antibiotics in the outpatient settings and the use of antibiotics in animal husbandry and agriculture.
 

MECHANISMS OF ACTION OF ANTIMICROBIAL AGENTS

In order to appreciate the mechanisms of resistance, it is important to understand how antimicrobial agents act. Antimicrobial agents act selectively on vital microbial functions with minimal effects or without affecting host functions. Different antimicrobial agents act in different ways. The understanding of these mechanisms as well as the chemical nature of the antimicrobial agents is crucial in the understanding of the ways how resistance against them.

CLASSIFICATION OF ANTI-MICROBIAL AGENTS- • 

Bacteriostatic antimicrobial- These agents only inhibit the growth or multiplication of the bacteria giving the immune system of the host time to clear them from the system. Complete elimination of the bacteria in this case, therefore, is dependent on the competence of the immune system.

• Bactericidal agents- They kill the bacteria and therefore with or without a competent immune system of the host, the bacteria will be dead. •

• However, the mechanism of action of antimicrobial agents can be categorized further based on the structure of the bacteria or the function that is affected by the agents. These include generally the following:

• Inhibition of the cell wall synthesis

• Inhibition of ribosome function

• Inhibition of nucleic acid synthesis

• Inhibition of foliate metabolism

• Inhibition of cell membrane function

MECHANISMS OF ANTIMICROBIAL RESISTANCES

 Prior to the 1990s, the problem of antimicrobial resistance was never taken to be such a threat to the management of infectious diseases. But gradually treatment failures were increasingly being seen in health care settings against first-line drugs and second-line drugs or more. Microorganisms were increasingly becoming resistant to ensure their survival against the arsenal of antimicrobial agents to which they were being bombarded. They achieved this through different means but primarily based on the chemical structure of the antimicrobial agent and the mechanisms through which the agents acted. The resistance mechanisms, therefore, depend on which specific pathways are inhibited by the drugs and the alternative ways available for those pathways that the organisms can modify to get a way around in order to survive.

Intrinsic or natural or passive whereby microorganisms naturally do not posses target sites for the drugs and therefore the drug does not affect them or they naturally have low permeability to those agents because of the differences in the chemical nature of the drug and the microbial membrane structures especially for those that require entry into the microbial cell in order to effect their action. An example of natural resistance is Pseudomonas aeruginosa, whose low membrane permeability is likely to be a main reason for its innate resistance to many antimicrobials. Other examples are the presence of genes affording resistance to self-produced antibiotics, the outer membrane of Gram-negative bacteria, absence of an uptake transport system for the antimicrobial or general absence of the target or reaction hit by the antimicrobial.

• Acquired or active resistance, the major mechanism of antimicrobial resistance, is the result of a specific evolutionary pressure to develop a counterattack mechanism against an antimicrobial or class of antimicrobials so that bacterial populations previously sensitive to antimicrobials become resistant. This type of resistance results from changes in the bacterial genome. Resistance in bacteria may be acquired by a mutation and passed vertically by selection to daughter cells . More commonly, resistance is acquired by horizontal transfer of resistance genes between strains and species. Exchange of genes is possible by transformation, transduction or conjugation. Acquired resistance mechanisms can occur through various ways.

Mechanisms for acquired resistance -

• the presence of an enzyme that inactivates the antimicrobial agent
• the presence of an alternative enzyme for the enzyme that is inhibited by the antimicrobial agent
• a mutation in the antimicrobial agent’s target, which reduces the binding of the antimicrobial agent
• post-transcriptional or post-translational modification of the antimicrobial agent’s target, which reduces binding of the antimicrobial agent
• reduced uptake of the antimicrobial agent
• active efflux of the antimicrobial agent overproduction of the target of the antimicrobial agent